PROJECT SUMMARY A toxic stress response can result from exposure to extreme stressors in early childhood, such as poverty, violence or parental mental illness. Persistent elevation of the stress response system causes physiological disruptions that can result in alterations to brain architecture and neuroendocrine, immune, metabolic and cardiovascular functioning. Studies from animals and maltreated children demonstrate that the presence of a nurturing caregiver can buffer against the physiological disruptions associated with a toxic stress response; however, the specific positive caregiving characteristics that best promote a protective relationship in humans remain largely unexplored, particularly in families living in high-risk environments. Framed by an ecobiodevelopmental model, the proposed study employs a cross-sectional design to describe and examine relationships among past maternal experiences with caregiving, current caregiving patterns, and children's indicators of a toxic stress response in a multiethnic, urban sample of maternal-child dyads with children at early school age. The first aim of this study is to describe physiological (hair cortisol, salivary c-reactive protein and inflammatory cytokines, blood pressure), health (body mass index, growth delay) and behavioral (internalizing and externalizing behaviors) indicators of a toxic stress response in children. The second aim of this study is to describe maternal caregiving characteristics in the sample, including past maternal experiences with caregiving (adverse childhood experiences, family strengths) and current caregiving patterns (parental reflective functioning, parenting behaviors). The third aim is to examine correlations among past maternal experiences with caregiving, current caregiving patterns, and indicators of a toxic stress response in children. The results of this study will provide essential preliminary data to support future studies designed to examine causal relationships between maternal characteristics and indicators of a toxic stress response in children, and may inform the development of interventions aiming to promote health and reduce disparities within families at risk for toxic stress. The proposed training plan includes coursework and a variety of scholarly and research activities to establish a strong foundation in nursing science and concepts related to the study, including maternal-child relationships, health disparities and social determinants of health. The training plan also includes specific experiences designed to promote extensive knowledge of the stress response system and develop my expertise in research methods, especially with complex families living in challenging community environments. Aligned with NINR's strategic plan to promote health and reduce disparities in minority and underserved populations, the proposed study and training plan will provide an essential foundation for a career in nursing research focused on investigating protective factors for toxic stress in families living with adversity.